Method for predicting prognosis of patient with cancer or inflammatory disease

Abstract

Novel means that enables prediction of prognosis of a patient with cancer or inflammatory disease is disclosed. In the method for prediction of prognosis of a patient with cancer or inflammatory disease according to the present invention, the expression level of the FROUNT gene in a sample collected from the patient is measured. Since FROUNT is a poor prognostic factor, the lower the expression level of the FROUNT gene is, the better the prognosis in the patient is predicted to be. Or, the expression level of the CC chemokine receptor/ligand gene in a sample collected from the patient is measured. Since the CC chemokine receptor/ligand gene such as CCR2 or CCR5 is a good prognostic factor, the higher the expression level of the CC chemokine receptor/ligand gene is, the better the prognosis in the patient is predicted to be.

The invention claimed is: 
     
       1. A method for predicting prognosis of a patient with cancer or inflammatory disease and treating the patient, said method comprising:
 measuring an expression level of FROUNT gene in a sample collected from said patient; 
 determining prognosis of said patient by determining whether the expression of the FROUNT gene in the sample is detected, wherein a poor prognosis of said patient is indicated when an expression of the FROUNT gene is detected; and 
 administering an effective amount of a FROUNT inhibitor or a CC chemokine receptor/ligand inhibitor to the patient determined to have a poor prognosis. 
 
     
     
       2. The method according to  claim 1 , wherein the measurement of the expression level(s) is carried out by immunohistological staining. 
     
     
       3. The method according to  claim 1 , which is a method for predicting prognosis of a cancer patient. 
     
     
       4. The method according to  claim 1 , which is a method for predicting prognosis of a cancer patient at stage II or more advanced stage. 
     
     
       5. The method according to  claim 1 , wherein said CC chemokine receptor/ligand gene is at least one selected from the group consisting of the CCR2 gene and the CCR5 gene. 
     
     
       6. The method according to  claim 1 , wherein said sample is a lesion tissue sample. 
     
     
       7. The method according to  claim 1 , wherein said cancer is lung cancer. 
     
     
       8. A method for predicting prognosis of a patient with cancer or inflammatory disease, said method comprising:
 measuring an expression level of FROUNT gene and an expression level of the CC chemokine receptor/ligand gene in a sample collected from said patient, said CC chemokine receptor/ligand gene being at least one selected from the group consisting of the CCR2 gene, CCR5 gene, CCL2 gene, and the CCL5 gene; 
 comparing the expression level of the CC chemokine receptor/ligand gene measured in said sample with a predetermined CC reference value; 
 carrying out the following step (i) or (ii): 
 (i) determining prognosis of said patient as good when the measured expression level is not less than the CC reference value, or 
 (ii) comparing the expression level of the FROUNT gene measured in said sample with a predetermined FROUNT reference value when the measured expression level of the CC chemokine receptor/ligand gene is less than the predetermined CC reference value, and determining prognosis of said patient as poor if the measured expression level of the FROUNT gene is not less than the FROUNT reference value, or as good if the measured expression level of the FROUNT gene is less than the FROUNT reference value; and 
 administering an effective amount of a FROUNT inhibitor or a CC chemokine receptor/ligand inhibitor to the patient determined to have a poor prognosis. 
 
     
     
       9. The method according to  claim 8 , wherein the measurement of the expression level of the FROUNT gene is carried out by immunohistological staining. 
     
     
       10. The method according to  claim 8 , wherein said CC reference value and said FROUNT reference value are values calculated by subjecting data on the expression level of the FROUNT gene, data on the expression level of the CC chemokine receptor/ligand gene, and prognostic data in a group of known patients with cancer or inflammatory disease to recursive partitioning analysis. 
     
     
       11. A method for predicting prognosis of a patient with cancer or inflammatory disease, said method comprising:
 measuring an expression level of FROUNT gene and an expression level of the CC chemokine receptor/ligand gene in a sample collected from said patient, said CC chemokine receptor/ligand gene being at least one selected from the group consisting of the CCR2 gene, CCR5 gene, CCL2 gene, and the CCLS gene; 
 comparing the expression level of the CC chemokine receptor/ligand gene measured in said sample with a predetermined CC reference value; 
 carrying out the following step (i) or (ii): 
 (i) determining prognosis of said patient as good when the measured expression level is not less than the CC reference value, or 
 (ii) applying the measured expression levels of the FROUNT gene and the CC chemokine receptor/ligand gene to the following Equation 1 when the measured expression level is less than the CC reference value, and determining prognosis of said patient as poor if h>0, or as good if h<0; and 
 administering an effective amount of a FROUNT inhibitor or a CC chemokine receptor/ligand inhibitor to the patient determined to have a poor prognosis:
     h=β   CC ×([ CC ]−[ CC ] m )+ P   FROUNT ×([FROUNT]−[FROUNT] m )  Equation 1
 
 
 
       wherein
 [CC] m : a log value of the expression level of the CC chemokine receptor/ligand gene in the sample; 
 [CC] m : a mean or a median of log values of the expression levels of the CC chemokine receptor/ligand gene measured in a known patient population; 
 [FROUNT]: a log value of the expression level of the FROUNT gene in the sample; 
 [FROUNT] m : a mean or a median of log values of the expression levels of the FROUNT gene measured in a known patient population; 
 βcc: a coefficient calculated by applying the Cox proportional hazard model using as a variable log values of the expression levels of the CC chemokine receptor/ligand gene to prognostic data in a known patient population; and 
 βFROUNT: a coefficient calculated by applying the Cox proportional hazard model using as a variable log values of the expression levels of the FROUNT gene to prognostic data in a known patient population.